Accuracy of cervical smears in predicting the grades of cervical intraepithelial neoplasia

This is a retrospective study carried out to assess the correlation between the cytology and histology of cervical intraepithelial neoplasia in 1325 women. A poor correlation between the cytologic and histologic diagnosis of the various grades of CIN was shown. Forty-one percent of smears with repeated borderline change and 50% of those predicting CIN1 showed a higher grade of CIN on histology. The overall apparent false negative rate of cervical smears for high grade CIN (CIN2 and CIN3) was 19% and for CIN3 alone was only 3%. It is therefore concluded that there is a consistent tendency for cervical cytology to underestimate the severity of histologic lesions and it is therefore important that the clinicians ensure adequate follow-up of patients whose smears show a lesser degree of abnormality.     

Screening and treatment for cervical intraepithelial neoplasia (CIN) in HIV-infected women

BACKGROUND: To determine: 1) whether the pathology correlates with the degree of immunosuppression, 2) whether there is a relation between pathology and antiretroviral therapies, 3) whether Papanicolau (Pap) smears correlate with colposcopic and histologic findings, 4) whether there is rapid genital disease progression after standard gynaecologic care. METHODS: Retrospective study. Immunologic, gynaecologic and virologic data were extracted either from patients charts or from laboratory testing. RESULTS: At first visit Pap smears resulted normal in 43.7% of the women, 8.4% of the patients had reactive and reparative changes, 2.8% atypical cells of undetermined significance, 33.8% low-grade squamous intraepithelial lesions and 11.3% high-grade squamous intraepithelial lesions. Patients with a normal PAP smear had higher CD4 cell count (318+/-191 cells/mL) compared to patients with squamous intraepithelial lesions (297+/-116 cells/mL) but the difference was not statistically significant (Mann-Whitney test). The distribution of cervical dysplasia was found to be similar regardless of antiretroviral therapy (chi(2) test). The sensitivity and specificity of Pap tests for detecting CIN were 94 and 80%. Twenty-two per cent of surgically treated women had persistent or recurrent disease. CONCLUSIONS: Lower CD4+ cell counts are not predictive of the presence of cervical dysplasia. All HIV-infected women, independently from their immunological and clinical conditions, need regular Pap smears with appropriate follow-up for abnormal cervicovaginal cytology, this could prevent nearly all deaths from cervical cancer.     

Behavior of cervical intraepithelial neoplasia (CIN) associated with various human papillomavirus (HPV) types

Summary 201 cervical punch biopsies which showed CIN lesions and were obtained between 1967 to 1977 from Falu Hospital patients, with long-term follow-up data were examined histologically and by DNA typing for human papillomavirus (HPV). We used in situ hybridization for HPV types 6, 11, 16, 18, 31 and 33 and related our findings to the behaviour of the lesion (103 regressed spontaneously and 98 progressed, some of them to invasive cervical carcinoma). There was evidence of HPV infection in 75.6% (152/201) of these lesions on histological examination, and in 53.2% (107/201) on in situ DNA hybridization. Lesions positive for HPV by both methods occurred in the younger age group (Pearson’s correlation coefficient,P=0.008). HPV 16 was found in 51/152 (33.6%) of the HPV lesions, HPV in 12.5%, and HPV 33 in 8.5% HPV 16 was highly significantly (P=0.0001), and HPV 18 and HPV 33 were significantly (P=0.008 andP=0.007, respectively) associated with increasing grades of CIN. Progression to invasive carcinoma was directly (and regression inversely) correlated with the severity of CIN in the first biopsy (P=0.005). Almost 74% (17/23) of the HPV-CIN III lesions progressed, while only 25% of the HPV-NCIN lesions (6/24) did so. The progression rate was 84.6% for HPV 33 lesions and 52.9% for HPV 16. On the other hand, progression was less common with HPV 6 (25%), and HPV 31 (30.0%). Histological grade and HPV type appear to be of value as prognostic indices. An erratum to this article is available at .     

2006 consensus guidelines for the management of women with cervical intraepithelial neoplasia or adenocarcinoma in situ

A group of 146 experts representing 29 organizations and professional societies met Sept. 18-19, 2006, in Bethesda, MD, to develop revised evidence-based, consensus guidelines for managing women with abnormal cervical cancer screening tests. The management of low-grade cervical intraepithelial neoplasia (CIN) grade 1 has been modified significantly. Previously, management depended on whether colposcopy was satisfactory and treatment using ablative or excisional was acceptable for all women with CIN 1. In the new guidelines, cytological follow-up is the only recommended management option for women with CIN 1 who have low-grade referral cervical cytology, regardless of whether the colposcopic examination is satisfactory. Treatment is particularly discouraged in adolescents. The basic management of women in the general population with CIN 2,3 underwent only minor modifications, but options for the conservative management of adolescents with CIN 2,3 have been expanded. Moreover, management recommendations for women with biopsy-confirmed adenocarcinoma in situ are now included.     

宫颈上皮内瘤样病变Ⅲ级治疗与预后分析

目的探讨宫颈上皮内瘤样病变Ⅲ级(CINⅢ)的治疗方法。方法对1972年至1998年在我院治疗的宫颈原位癌48例和宫颈重度不典型增生28例进行回顾性分析。结果原位癌患者中,行次广泛全子宫切除术的29例和全子宫切除术的11例,术后均无复发;6例行宫颈锥形切除术,1例术后14年再次发生原位癌;重度不典型增生的患者,行子宫切除术和锥切术患者均无复发。结论宫颈CINⅢ发病年龄出现年轻化趋势,全子宫切除术与次广泛全子宫切除术预后相近,全子宫切除术可作为原位癌患者的首选治疗方法;单纯宫颈锥切术有术后复发可能,术后应严密随访;重度不典型增生可行宫颈锥切术或LEEP手术,术后应定期随诊。     

Prognostic significance of herpes simplex virus antibody status in women with cervical intraepithelial neoplasia (CIN)

A total of 107 women with abnormal cervical smears showing cytological changes consistent with cervical intraepithelial neoplasia (CIN) 1 or CIN 2 were kept under regular cytological, colposcopic, virological and serological surveillance for an average of 18 months (range 9 months-3 years). Regression of the cervical lesion was noted in 31 (29%) and progression to CIN 3 in nine women (8.4%). We found a positive correlation between the presence of type 2 antibody and progression of CIN 1 and 2 to CIN 3 and a negative association with the presence of type 1 antibody and suggest the antibody status of a woman with CIN 1 or CIN 2 may provide a useful basis for follow-up. We found no association between the outcome of the cervical lesion and active infection with herpes simplex or cytomegalovirus or any other infectious agent or sex-related factors.     

Prognostic significance of herpes simplex virus antibody status in women with cervical intraepithelial neoplasia (CIN)

Summary. A total of 107 women with abnormal cervical smears showing cytological changes consistent with cervical intraepithelial neoplasia (CIN) 1 or CIN 2 were kept under regular cytological, colposcopic, virological and serological surveillance for an average of 18 months (range 9 months-3 years). Regression of the cervical lesion was noted in 31 (29%) and progression to CIN 3 in nine women (8.4%). We found a positive correlation between the presence of type 2 antibody and progression of CIN 1 and 2 to CIN 3 and a negative association with the presence of type 1 antibody and suggest the antibody status of a woman with CIN 1 or CIN 2 may provide a useful basis for follow-up. We found no association between the outcome of the cervical lesion and active infection with herpes simplex or cytomegalovirus or any other infectious agent or sex-related factors.     

The basement membrane in the carcinoma in situ of the cervix: A morphological study

A morphological study of the basement membrane in the carcinoma in situ of the cervix has been carried out.Undifferentiated carcinoma in situ that arises usually from the squamocolumnar junction and which extends into the endocervical canal, always shows a continuous and clearly delineated basement membrane, which runs parallel to the basal layer. It has a homogeneous appearance. The hemidesmosomes attached to the lamina propria are quite normal and there are no slender protrusions from basal cells into the lamina propria.Differentiated carcinoma in situ, that originates in the squamous epithelium of the portio, may extend either in the direction of vagina, or towards the endocervical canal. It is always underlined by a basement membrane loosely constituted of irregular or fragmented reticular fibers; it frequently looses its homogeneous appearance and may be dehiscent or duplicated. Basal cells send down small pseudopods or threadlike extensions into the lamina propria.The authors suggest that in the management of carcinoma in situ of the cervix, one should take into consideration the direction of spread and the stroma-invasion potential of the carcinoma. These histologic patterns carry with them a very important morphologic implication, namely ‘cells differentiation’ of the carcinoma.     

Cryosurgical treatment of cervical intraepithelial neoplasia (CIN III) in 102 patients

Results of cryosurgical treatment in 102 patients with a histologically confirmed diagnosis of severe dysplasia or carcinoma in situ of the uterine cervix (CIN III) are presented. The colposcopic evaluation performed in all patients required full visualization of the squamocolumnar junction. In 95 of the 102 patients no significant cytological abnormalities were found during the follow-up period, which amounts to a success rate of 93%. In seven patients (7%) treatment was considered to have failed because cervical smears persistently suggested CIN II or III. In five of them this was in all probability due to a residual lesion, since the abnormal smears occurred within 12 weeks after cryosurgery. It is concluded that in selected cases cryosurgery is a safe alternative for conisation in the treatment of CIN III. However, thorough colposcopic expertise is essential for adequate preoperative screening, as is careful selection of patients, and the latter may result in the withholding of cryosurgical therapy from 30% of patients with CIN III.     

Conservative management of cervical intraepithelial neoplasia (CIN(2-3)) in pregnant women

The management of cervical intraepithelial neoplasia (CIN(2-3)) diagnosed during pregnancy was the subject of this study. Two hundred and eight pregnant women with an abnormal cytology were assessed in our unit over a 10-year period. The age of the patients ranged from 20 to 45 (mean 28) years. Seventy-eight of these women were histologically proven to have CIN(2-3). All patients were followed up every 8-10 weeks by cytology and colposcopy during pregnancy and reassessed 8-12 weeks postpartum. The disease persisted in 30 cases (38.4%), whereas in the remaining 48 cases it regressed to CIN(1). No case of invasive disease developed during the follow-up period in these pregnant patients. Conservative management of CIN(2-3) during pregnancy is acceptable, but close follow-up and colposcopic expertise are necessary.     

宫颈鳞癌和上皮内瘤变组织中TRF1、TRF2及HPV16、HPV18的检测及其意义

目的研究端粒结合蛋白TRF1、TRF2在宫颈鳞癌发生发展中的作用并分析HPV16、HPV18感染与TRF1、TRF2蛋白表达的关系。方法随机选择南华大学附属第一医院病理科2005年9月至2006年10月期间的组织石蜡块标本共86例,采用原位杂交方法检测HPV16、HPV18在15例正常宫颈上皮、36例宫颈上皮内瘤变(CIN)和35例宫颈鳞癌组织中的感染情况;采用免疫组化方法检测所有组织标本中TRF1、TRF2蛋白的表达。结果(1)HPV16、HPV18阳性感染率CIN组[63.9%(23/36)]和宫颈鳞癌组[97.1%(34/35)]显著高于正常组[20.0%(3/15)](χ2=30.639,P<0.01)。(2)TRF1阳性表达率宫颈鳞癌组[40.0%(14/35)]显著低于CIN组[63.9%(23/36)]和正常组[86.7%(13/15)](χ2=10.237,P<0.01);CINⅢ组[42.9%(6/14)]显著低于CINⅠ组[90.0(9/10)](χ2=5.531,P<0.01)。TRF2阳性表达率宫颈鳞癌组[80.0%(28/35)]显著高于CIN组[52.8%(19/36)]和正常组[...     

阴道上皮内瘤变与宫颈上皮内瘤变的相关性及其诊治的初步研究

目的 探讨阴道上皮内瘤变(VAIN)与宫颈上皮内瘤变(CIN)的相关性及其诊断和治疗.方法 回顾性分析35例VAIN患者的临床表现、阴道脱落细胞学、人乳头状瘤病毒(HPV)感染以及治疗方法等资料.结果患者平均年龄43.9岁.VMN Ⅰ、VAIN Ⅱ和VMNⅢ分别占52%(18/35)、34%(12/35)和14%(5/35).VAINⅢ在年龄≤40岁者和>40岁者中分别为8%(1/13)和18%(4/22).69%(24/35)有CIN病史,17%(6/35)有宫颈癌病史.CIN Ⅰ、CIN Ⅱ～Ⅲ和宫颈癌中分别有3/9、53%(8/15)和4/6发生VAINⅡ～Ⅲ.87%(13/15)的VMN Ⅰ患者高危型HPV-DNA阳性,VAIN Ⅱ和VAINⅢ中的阳性率均为100%.97%(33/34)液基薄片检测提示细胞学检查结果异常.86%(30/35)病变位于阴道上1/3.19例患者进行了治疗,其中手术切除占74%(14/19),局部用药占16%(3/19),腔内放疗占11%(2/19).9例随访者VMN病变均出现逆转.结论 VMN 临床特点与CIN相似,CIN诊断和治疗的原则也可适用于VAIN.     

人乳头状瘤病毒感染的宫颈上皮内肿瘤和宫颈鳞状细胞癌中的间期细胞遗传学分析

目的探讨人乳头状瘤病毒（HPV）感染的宫颈上皮内肿瘤（CIN）和宫颈鳞状细胞癌中的间期细胞遗传学改变。方法对HPV感染的9例CIN（其中CINⅠ2例、CINⅡ3例、CINⅢ4例）和4例宫颈鳞状细胞癌的石蜡包埋组织，应用组织切片间期细胞核原位杂交技术检测染色体11、16、17和X的数目异常，3例正常宫颈鳞状上皮作为对照。结果除2例CINⅠ的患者中被检染色体无异常外，其余11例（包括3例CINⅡ，4例CINⅢ以及4例宫颈浸润性鳞状细胞癌）均出现1条或多条被检测染色体的异常，其中4例分别发现了染色体11、17和X单体型。结论HPV16感染与11、16、17及X号染色体数目异常有关，而HPV DNA与宿主细胞染色体整合可能导致染色体的单体型出现。     

Recombinant human interferon gamma in the treatment of cervical intraepithelial neoplasia (CIN) associated with human papillomavirus (HPV) infection

Human papillomavirus (HPV) proteins E6 & E7 are considered to be the constitutively expressed neoantigens in a vast majority of cervical squamous intraepithelial lesions and cancers. Data available from in-vitro, animal, and small clinical trials suggest that the immunological properties of interferon gamma might enhance early viral protein presentation, thus stimulating a cytotoxic response. In order to study this effect in vivo we undertook a trial in which 20 women with a definite diagnosis of cervical intraepithelial neoplasia (CIN) grade I or II with coexistent high-risk HPV infection (detected by the Hybrid Capture System) underwent four months observation followed by intracervical administration of INFgamma in cases without spontaneous regression (17 cases). Human recombinant interferon gamma 1-b (Imukin) was administered intracervically four times in equal doses in two-day intervals to a total dose of 6,000,000 IU. The results of therapy were verified by punch biopsy evaluation and HPV-DNA testing two months after completion, and revealed a complete response in nine women (complete regression of CIN and remission of HPV infection in 53% of treated cases) and partial response in four cases (lower grade of CIN or/and remission of HPV infection--23.5%). The differences between spontaneous (before treatment) and treatment-related regressions were significant at p < 0.05. We conclude that in selected cases (mainly young women who have not completed their procreation and are compliant with the therapy) a conservative approach to CIN management with intracervical IFNgamma injections seems to be a valuable method.     

Macrophages, inflammation and risk of cervical intraepithelial neoplasia (CIN) progression--clinicopathological correlation

OBJECTIVE: To evaluate the population of macrophages during the cervical malignant transformation and its influence in CIN outcome. METHODS: Biopsies from 26 normal cervix, 28 low-grade (LSIL), 30 high grade squamous intraepithelial lesions (HSIL) and 28 squamous cell carcinomas (SCC) were stained by H&E to assess inflammation and by immunohistochemistry with anti-CD68 to detect macrophages. The macrophage count was corrected for the epithelial and stromal compartments using appropriate software. Clinical and prospective follow-up data were also available. RESULTS: We identified that macrophage count increased linearly with disease progression (median count per case at x200 magnification: normal, 5.1; LSIL, 5.5; HSIL, 9.9; SCC, 14.5; P<0.001), that inflammation also increased (moderate-intense inflammation present in 25%, 46.1%, 58.4% and 89.3% of normal, LSIL, HSIL and SCC, respectively; P<0.001) and that macrophage count was independently associated with the lesion grade (P<0.001). Moreover, macrophages showed an increasing migration into the epithelium along with the progression of CIN to invasive cancer. Of the 24 LSIL cases with information available, followed-up for 805+/-140 days, 16 regressed, 6 persisted and 2 progressed. Age, high-risk HPV or inflammation were not risk factors for persistent/progressed LSIL in our cohort. However, LSIL that persisted or progressed showed a higher macrophage count (median of 10.8) than lesions that regressed (7; P=0.031). CONCLUSIONS: The study on macrophages offers a potential approach for cervical cancer treatment, since macrophages are closely related to progression of CIN, and can be used as an applicable marker of such a risk.     

miR-218下调与宫颈上皮内瘤变患者HPV病毒感染关系的研究

目的:探讨小分子RNA-218(miR-218)下调与宫颈上皮内瘤变(CIN)患者人乳头瘤病毒(HPV)感染的关系。方法:选择78例宫颈上皮内瘤变(CIN)患者,其中CINⅠ22例(28.2%),CINⅡ27例(34.6%),CINⅢ29例(37.2%),逆转录聚合酶链反应(RT-PCR)检测miR-218的表达,GenoArray测试工具包检测组织标本中HPV的表达。结果:miR-218在高危型HPV感染患者中的含量低于低危型HPV感染者,CINⅡ、Ⅲ患者miR-218含量比CINⅠ患者低。结论:高危型HPV感染患者中miR-218表达降低,提示miR-218可能是宫颈癌发生的重要因素。     

The management and follow-up of patients with high-grade cervical glandular intraepithelial neoplasia

Maini M, Lavie O, Comerci G, Cross PA, Bolger B, Lopes A, Monaghan JM. The management and follow-up of patients with high-grade cervical glandular intraepithelial neoplasia. Int J Gynecol Cancer 1998; 8 : 287–291.
The purpose of this study was to evaluate if the status of the margins on large loop excision of the transformation zone (LLETZ) can predict the presence of residual cervical glandular intraepithelial neoplasia (CGIN) and to assess the efficacy of cervical conization as primary management of CGIN. Between January 1989 and March 1997 fifty patients with a diagnosis of CGIN made by LLETZ were treated in the Department of Gynaecological Oncology at the Queen Elizabeth Hospital, Gateshead. Presence or absence of CGIN at cone margins, results of cervical cytological examinations before and following conization, colposcopic examination, and results of histopathologic assessment of any surgical specimens taken after initial cone biopsy were analyzed in this study. Of the 50 patients with CGIN, managed by conization, in 34 (68%) CGIN was present at the surgical margins and in 16 (32%) the margins were clear. Eleven (32.3%) patients with CGIN at the margins of excision had evidence of residual disease and there was only one of the 16 (6.25%) patients with clear margins ( P = 0.03). Two cases of invasive adenocarcinoma were identified in the group of patients with positive margins. In a mean follow-up time of 32.35 months, no case of invasive carcinoma was identified in the completely excised group. In our retrospective study LLETZ was found to be an adequate primary management for CGIN, and the excision margin status of the LLETZ specimen did appear to be a prognostic factor for residual disease.